Thursday, June 15, 2023

EID Journal: Low Susceptibility of Pigs against Experimental Infection with HPAI Virus H5N1 Clade 2.3.4.4b

 

#17,495

Last month, in Netherlands: Zoonoses Experts Council (DB-Z) Risk Assessment & Warning of Swine As `Mixing Vessels' For Avian Flu, we looked at concerns that avian H5N1 could increase its pandemic threat by spreading (and evolving) in farmed swine.

That report was followed a week later by a report (see Study: Seroconversion of a Swine Herd in a Free-Range Rural Multi-Species Farm against HPAI H5N1 2.3.4.4b Clade Virusat a `mixed species' farm (poultry & swine) in Italy.

Similar concerns were voiced 2 months ago, in the ECDC/EFSA Avian Influenza Overview December 2022 – March 2023 which warned:

The additional reports of transmission events to and potentially between mammals, e.g. mink, sea lion, seals, foxes and other carnivores as well as seroepidemiological evidence of transmission to wild boar and domestic pigs, associated with evolutionary processes including mammalian adaptation are of concern and need to be closely followed up.

This is not a new concern (see below), but HPAI H5's recent affinity for spilling over into mammals has raised the stakes. A few past reports on H5 in swine include:

WHO H5N1 detected in pigs in China (2004)

EID Journal: Asymptomatic H5N1 In Pigs (2010)

An Unusual Report Of H5N1 in Pigs (Indonesia 2016)

Sci. Rpts.: Evidence Of H5N1 Exposure In Domestic Pigs - Nigeria (2018)

While H5 infection in pigs appears rare, between extremely limited testing, and the fact that H5N1 tends to be asymptomatic (or mildly symptomatic) in pigs, it may be more common than we realize. 

Yesterday the CDC's EID journal published a report on experimental infection of pigs with an H5N1 clade 2.3.4.4b virus conducted by the Friedrich-Loeffler-Institut in Germany. 

Reassuringly they found that exposed pigs demonstrated only a low susceptibility to infection with the virus strain used. 

At first glance, this would seem to be great news, but it comes with a significant caveat.  The authors  wrote (underlining mine):

Overall, we conclude that pigs are unlikely vehicles in transmitting this genotype of HPAI virus H5N1 clade 2.3.4.4b among pigs and across interfaces.

Followed by:

However, considering the ongoing massive panzootic of this virus, a plethora of new genotypes of the circulating strain is emerging, with possibly higher permissiveness for pigs.  

Since HPAI H5N1 continues to evolve rapidly (see H5N1: The Only Constant is Change), it is reasonable to assume the properties of the strain used in this study could differ from the scores of other genotypes that currently circulate around the globe, and those that will inevitably follow. 

But for now, this is relatively encouraging news.

Some excerpts from the report follow, after which I'll have a brief postscript.

Research Letter
Low Susceptibility of Pigs against Experimental Infection with HPAI Virus H5N1 Clade 2.3.4.4b

Annika Graaf , Ronja Piesche, Julia Sehl-Ewert, Christian Grund, Anne Pohlmann, Martin Beer, and Timm Harder
Author affiliation: Friedrich-Loeffler-Institut, Greifswald–Insel Riems, Germany

Abstract

We found that nasal and alimentary experimental exposure of pigs to highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b was associated with marginal viral replication, without inducing any clinical manifestation or pathological changes. Only 1 of 8 pigs seroconverted, pointing to high resistance of pigs to clade 2.3.4.4b infection.
 

Spread of highly pathogenic avian influenza (HPAI) virus H5N1 clade 2.3.4.4b of the goose/Guangdong (gs/GD) lineage, has exacerbated since early 2022 into a panzootic (1). Regional enzootic status in wild bird populations in Europe and North America, with lethal courses of HPAI virus infection in some species, produced large numbers of wild bird carcasses, easy prey for raptors and scavengers. Exposure of terrestrial carnivores and marine mammals resulted in sporadic infections, some of those terminating with fatal encephalitis (2). Frequent spill-over events, rather than consistent mammal-to-mammal transmission, were at the basis of these cases (Figure, panel A). However, recently reported HPAI outbreaks among sea lions along the Pacific coast of South America and an outbreak in a mink farm in Spain (3) may constitute first examples of avian-independent transmission chains and increase public health concerns about zoonotic transmissions of this virus. Still, the total of 11 human cases globally reported for the currently dominating H5N1 2.3.4.4b lineage did not point toward increased zoonotic propensity (4).

Possible adaption of avian influenza virus (AIV) to mammalian livestock hosts and subsequent human exposure is of particular concern. In this respect, the role of pigs as a “mixing vessel” for HPAI viruses is largely unresolved. AIV can potentially be transmitted to pigs, and further reassortment with swine influenza A viruses (swIAVs) may contribute to the emergence of pandemic strains. Rare and subclinical infections of pigs with gs/GD HPAI virus have been confirmed serologically in Vietnam, Thailand, and France (5) and virologically in Indonesia (clades 2.1.1 and 2.1.3), Nigeria (clade 2.3.2.1c), China (clade 2.3.4), and Italy (clade 2.3.4.4.b) (68).

For our study, we purchased 4-month-old pigs (6 male, 4 female) from a conventional pig holding in Germany and exposed them nasally or by the alimentary route to high doses of the recent avian-derived HPAI virus H5N1 2.3.4.4b isolate A/chicken/Germany/AI04286/2022 (genotype Ger-10.21-N1.5). The egg-grown isolate was closely related to a mammal case but lacked any mammalian-adaptive mutations (Figure, panel A). We inoculated 2 groups of 4 pigs each intranasally or by feeding 1 infected embryonated chicken egg per animal. One sentinel pig per group was associated at day 1 postinoculation to assess the transmission by direct contact to those inoculate

          (SNIP) 

In conclusion, only 1 of 8 pigs inoculated intranasally with HPAI virus H5N1 underwent transient, low-level infection that resulted in the presence of viral RNA in several tissue specimens and seroconversion at 14 dpi. In naturally infected wild mammals, this virus was prominently detected in the brain (2). Given the detection of viral RNA in the brain of 1 intranasally inoculated pig, it cannot be excluded that longer observation might have revealed continuing viral replication in the brain of this animal. Sialic acid α2,3-gal receptors dominate on porcine brain cells, which might have fostered replication of α2,3-adapted viruses, such as HPAI virus H5N1 (10).

Overall, we conclude that pigs are unlikely vehicles in transmitting this genotype of HPAI virus H5N1 clade 2.3.4.4b among pigs and across interfaces. However, considering the ongoing massive panzootic of this virus, a plethora of new genotypes of the circulating strain is emerging, with possibly higher permissiveness for pigs. Therefore, swine populations need to be part of HPAI virus surveillance programs, and periodic reassessment of prepandemic propensity of circulating HPAI virus H5N1 genotypes in the swine model is required.

Dr. Graaf is a veterinary virologist at the International (World Organisation for Animal Health/Food and Agriculture Organization of the United Nations) and National Reference Laboratory for Avian Influenza at the Institute of Diagnostic Virology at the Friedrich-Loeffler-Institute. Her research interests focus on avian and swine influenza A virus surveillance in Germany.



Everything we can say about the behavior and threat of avian flu is based on limited data, much of which is months (or even years) old by the time it gets published.  Our ability to monitor - in real time - what is happening with avian flu is severely limited. 

Not only are there vast swaths of the planet where little or no surveillance is being done, there are many countries that - for economic, societal, or political reasons -  are slow to share what they know.  

At the same time that H5N1's evolution has sped up, our ability to keep up has diminished.  And that is a dangerous position to be in.